Cirrhosis of the liver, a disease that is difficult to manage, is responsible for 1.2% of all U.S. deaths (1). Cirrhosis is most commonly caused by alcoholism, hepatitis B and hepatitis C, and fatty liver disease, but has many other possible causes such as non-alcoholic steatohepatitis, primary biliary cirrhosis, primary sclerosing cholangitis, autoimmune hepatitis, hereditary hemochromatosis, Wilson's disease, or alpha 1-antitrypsin deficiency.
Late stages of cirrhosis are characterized by portal hypertension and hepatic encephalopathy, terminal extrahepatic processes that result from fibrosis and vascular remodeling of the cirrhotic liver (2,3). These pathologies are superimposed on liver failure, which results from the inability of hepatocytes to adequately synthesize coagulation factors, conjugate and secrete bilirubin, and regulate metabolism (4-7). Generally, liver damage from cirrhosis cannot be reversed. Therefore, aggressive management can extend life, but the only definitive therapy for end-stage cirrhosis is orthotopic liver transplantation (8).
The cause of organ failure in cirrhosis is poorly understood, but impaired hepatocytes have both intrinsic damage and reside in an abnormal microenvironment (2-8). Studies have shown that somatic cells can be reprogrammed into pluripotent stem cells and fibroblasts or hepatocytes can be reprogrammed into other mature cell lineages following forced expression of selected transcription factors (9,10), although these methods have not been proven in vivo for the treatment of cirrhosis. Accordingly, there is a need for new methods to treat and/or manage cirrhosis and chronic liver disease.